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Amit A Vernekar, Gilles Berger, Anna E Czapar, Frank A Veliz, David I Wang, Nicole F Steinmetz, Stephen J Lippard
Efficient loading of drugs in novel delivery agents has the potential to substantially improve therapy by targeting the diseased tissue while avoiding unwanted side effects. Here we report the first systematic study of the loading mechanism of phenanthriplatin and its analogs into tobacco mosaic virus (TMV), previously used by our group as an efficient carrier for anticancer drug delivery. A detailed investigation of the preferential uptake of phenanthriplatin in its aquated form (∼2000 molecules per TMV particle versus ∼1000 for the chlorido form) is provided...
March 19, 2018: Journal of the American Chemical Society
Yang Wang, Xueping Kong, Wei Xu, Fengrui Jiang, Bao Li, Lixin Wu
A series of triol ligand [CH3 C(CH2 OH)3 ] covalently decorated polyoxometalates (POMs), which could be ascribed to the primary complexes with structural formulas {M2 [Mo2 O4 (CH3 C(CH2 O)3 )2 ]3 }2- (M = Cu2+ , Co2+ , Ni2+ , Zn2+ ), have been synthesized in organic solvents. Single-crystal X-ray structural analysis reveals that the synthesized polyanionic clusters are comprised of three {Mo2 } units and two divalent transition-metal ions connecting to each other in an alternating style, where all {Mo2 } blocks were covalently decorated by two triol ligands in the trans conformation...
March 19, 2018: Inorganic Chemistry
Qian Liang, Sainan Cui, Song Xu, Chao Yao, Mark J MacLachlan, Zhongyu Li
A novel triptycene-based covalent polymer (TCP) with a high surface area was constructed through the Suzuki coupling reaction. A very high photocatalytic H2 production rate of 50 670 μmol h-1 g-1 and superior photostability were achieved due to the intimate synergistic interactions between the TCP and Cd0.5Zn0.5S.
March 19, 2018: Chemical Communications: Chem Comm
Anna J Komor, Andrew J Jasniewski, Lawrence Que, John D Lipscomb
Covering: up to 2017The participation of non-heme dinuclear iron cluster-containing monooxygenases in natural product biosynthetic pathways has been recognized only recently. At present, two families have been discovered. The archetypal member of the first family, CmlA, catalyzes β-hydroxylation of l-p-aminophenylalanine (l-PAPA) covalently linked to the nonribosomal peptide synthetase (NRPS) CmlP, thereby effecting the first step in the biosynthesis of chloramphenicol by Streptomyces venezuelae. CmlA houses the diiron cluster in a metallo-β-lactamase protein fold instead of the 4-helix bundle fold of nearly every other diiron monooxygenase...
March 19, 2018: Natural Product Reports
Naixiang Zhai, Yanqin Lu, Yanzhou Wang, Xiuzhi Ren, Jinxiang Han
Circular RNA (circRNA) is a non-linear form of RNA derived from exonic, intronic, and exon-intron gene regions. circRNAs are characterized by covalent closed loops, highly stable nuclease resistance, and specific expression in species and developmental stages. CircRNA molecules have been identified as playing roles in the regulation of cell transcription, transcriptional expression after translation, interactions with microRNAs, and protein coding. A high stability and tissue- and disease-specific expression allow circRNAs to serve as potential biomarkers both for diseases and prognosis...
February 2018: Intractable & Rare Diseases Research
Breann L Brown, Julia R Kardon, Robert T Sauer, Tania A Baker
5-Aminolevulinic acid synthase (ALAS) catalyzes the first step in heme biosynthesis. We present the crystal structure of a eukaryotic ALAS from Saccharomyces cerevisiae. In this homodimeric structure, one ALAS subunit contains covalently bound cofactor, pyridoxal 5'-phosphate (PLP), whereas the second is PLP free. Comparison between the subunits reveals PLP-coupled reordering of the active site and of additional regions to achieve the active conformation of the enzyme. The eukaryotic C-terminal extension, a region altered in multiple human disease alleles, wraps around the dimer and contacts active-site-proximal residues...
March 5, 2018: Structure
Shruti Shukla, Yuvaraj Haldorai, Vivek K Bajpai, Arunkumar Rengaraj, Seung Kyu Hwang, Xinjie Song, Myunghee Kim, Yun Suk Huh, Young-Kyu Han
A sensitive electrochemical immunosensing platform for the detection of Cronobacter sakazakii was developed using a graphene oxide/gold (GO/Au) composite. Transmission electron microscopy showed that the Au nanoparticles, with an average size of < 30 nm, were well dispersed on the GO surface. For the detection of C. sakazakii, a polyclonal anti-C. sakazakii antibody (IgG) was covalently immobilized to the Au nanoparticles on the surface of the GO/Au composite coated glassy carbon electrode (GCE). The electrochemical sensing performance of immunofunctionalized GCE was characterized by cyclic voltammetry and differential pulse voltammetry...
March 8, 2018: Biosensors & Bioelectronics
Jinyoung Suh, Do-Hee Kim, Eun-Hee Kim, Sin-Aye Park, Jong-Min Park, Jeong-Hoon Jang, Su-Jung Kim, Hye-Kyung Na, Nam-Doo Kim, Nam-Jung Kim, Young Ger Suh, Young-Joon Surh
15-Deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ), one of the terminal products of cyclooxygenase-2-catalized arachidonic acid metabolism, has been shown to stimulate breast cancer cell proliferation and migration through Akt activation, but the underlying mechanisms remain poorly understood. In the present study, we investigated the effects of 15d-PGJ2 on the activity of PTEN, the inhibitor of the phosphoinositide 3-kinase (PI3K)-Akt axis, in human breast cancer (MCF-7) cells. Since the α,β-unsaturated carbonyl moiety in the cyclopentenone ring of 15d-PGJ2 is electrophilic, we hypothesized that 15d-PGJ2 -induced Akt phosphorylation might result from the covalent modification and subsequent inactivation of PTEN that has several critical cysteine residues...
March 14, 2018: Cancer Letters
Kevin Linka, Markus Hillgärtner, Mikhail Itskov
In recent experimental studies a possible damage mechanism of collagenous tissues mainly caused by fatigue was disclosed. In this contribution, a multi-scale constitutive model ranging from the tropocollagen (TC) molecule level up to bundles of collagen fibers is proposed and utilized to predict the elastic and inelastic long-term tissue response. Material failure of collagen fibrils is elucidated by a permanent opening of the triple helical collagen molecule conformation, triggered either by overstretching or reaction kinetics of non-covalent bonds...
March 14, 2018: Acta Biomaterialia
Kira Mergemeier, Matthias Lehr
Recently, we have described an HPLC-UV assay for the evaluation of inhibitors of plasma amine oxidase (PAO) using 6-(5-phenyl-2H-tetrazol-2-yl)hexan-1-amine (4) as a new type of substrate. Now we studied, whether this compound or homologues of it can also function as substrate for related amine oxidases, namely diamine oxidase (DAO), monoamine oxidase A (MAO A) and monoamine oxidase B (MAO B). Among these substances, 4 was converted by DAO with the highest rate. The best substrate for MAO A and B was 4-(5-phenyl-2H-tetrazol-2-yl)butan-1-amine (2)...
March 15, 2018: Analytical Biochemistry
Cláudia S Nóbrega, Bart Devreese, Sofia R Pauleta
The trihemic bacterial cytochrome c peroxidase from Escherichia coli, YhjA, is a membrane-anchored protein with a C-terminal domain homologous to the classical bacterial peroxidases and an additional N-terminal (NT) heme binding domain. Recombinant YhjA is a 50 kDa monomer in solution with three c-type hemes covalently bound. Here is reported the first biochemical and spectroscopic characterization of YhjA and of the NT domain demonstrating that NT heme is His63/Met125 coordinated. The reduction potentials of P (active site), NT and E hemes were established to be - 170 mV, + 133 mV and + 210 mV, respectively, at pH 7...
March 14, 2018: Biochimica et Biophysica Acta
Shahryar Khoshtinat Nikkhoi, Fatemeh Rahbarizadeh, Saeed Ranjbar, Sepideh Khaleghi, Alireza Farasat
Breast cancer is the leading cause of mortality among all cancers. HER2, human epidermal growth factor receptors type 2, a receptor tyrosine kinase that induces interminable cell proliferation, is overexpressed in 20-25 percent of breast cancers. In spite of significant progress in nanomedicine in the past decade, being subjected to genetic drift that hides many paramount epitopes has rendered targeting HER2 as a big challenge. In the present study, we developed monovalent and bivalent monospecific along with bivalent bispecific VHH targeting different epitopes on HER2, and showed that bivalent bispecific VHH has the highest affinity among other tested modalities...
March 14, 2018: Molecular Immunology
Nicole Welsch, Ashley C Brown, Thomas H Barker, L Andrew Lyon
Excessive bleeding and resulting complications are a major cause of death in both trauma and surgical settings. Recently, there have been a number of investigations into the design of synthetic hemostatic agents with platelet-mimicking activity to effectively treat patients suffering from severe hemorrhage. We developed platelet-like particles from microgels composed of polymers carrying polyethylene glycol (PEG) side-chains and fibrin-targeting single domain variable fragment antibodies (PEG-PLPs). Comparable to natural platelets, PEG-PLPs were found to enhance the fibrin network formation in vitro through strong adhesion to the emerging fibrin clot and physical, non-covalent cross-linking of nascent fibrin fibers...
March 2, 2018: Colloids and Surfaces. B, Biointerfaces
Lieselot De Smet, Gertjan Vancoillie, Peter Minshall, Kathleen Lava, Iline Steyaert, Ella Schoolaert, Elke Van De Walle, Peter Dubruel, Karen De Clerck, Richard Hoogenboom
Here, we introduce a novel concept for the fabrication of colored materials with significantly reduced dye leaching through covalent immobilization of the desired dye using plasma-generated surface radicals. This plasma dye coating (PDC) procedure immobilizes a pre-adsorbed layer of a dye functionalized with a radical sensitive group on the surface through radical addition caused by a short plasma treatment. The non-specific nature of the plasma-generated surface radicals allows for a wide variety of dyes including azobenzenes and sulfonphthaleins, functionalized with radical sensitive groups to avoid significant dye degradation, to be combined with various materials including PP, PE, PA6, cellulose, and PTFE...
March 16, 2018: Nature Communications
Jana Löwe, Aaron A Ingram, Harald Gröger
In recent years, the reductive amination of ketones in the presence of amine dehydrogenases emerged as an attractive synthetic strategy for the enantioselective preparation of amines starting from ketones, an ammonia source, a reducing reagent and a cofactor, which is recycled in situ by means of a second enzyme. Current challenges in this field consists of providing a broad synthetic platform as well as process development including enzyme immobilization. In this contribution these issues are addressed. Utilizing the amine dehydrogenase EsLeuDH-DM as a mutant of the leucine dehydrogenase from Exigobacterium sibiricum, a range of aryl-substituted ketones were tested as substrates revealing a broad substrate tolerance...
December 5, 2017: Bioorganic & Medicinal Chemistry
Scott K Shaw, Cynthia L Schreiber, Felicia M Roland, Paul M Battles, Seamus P Brennan, Simon J Padanilam, Bradley D Smith
The cell line OVCAR-4 was recently ranked as one of the most representative cell lines for high grade serous ovarian cancer (HGSOC). However, little work has been done to assess the susceptibility of OVCAR-4 cells and tumors to the more common types of molecular targeting. Proteome profiles suggest OVCAR-4 express high levels of integrin αvβ3 receptors. Using flow cytometry with fluorescent antibodies we determined that OVCAR-4 cells have high number of integrin αvβ3 receptors ([9.8 ± 2.5] × 104 /cell) compared to the well-characterized cell line U87-MG ([5...
March 6, 2018: Bioorganic & Medicinal Chemistry
Natércia Fernandes Brás, Diogo Santos-Martins, Pedro A Fernandes, Maria João Ramos
The excessive consumption of starch in human diets is associated with highly prevalent chronic metabolic diseases such as type 2 diabetes and obesity. α-glucosidase enzymes contribute for the digestion of starch into glucose and are thus attractive therapeutic targets for diabetes. Given that the active sites of the various families of α-glucosidases have different sizes and structural features, atomistic descriptions of the catalytic mechanisms of these enzymes can support the development of potent and selective new inhibitors...
March 16, 2018: Journal of Physical Chemistry. B
Vassilis E Papadopoulos, Georgia Nikolopoulou, Ivi Antoniadou, Antonia Karachaliou, Giovanna Arianoglou, Evangelia Emmanouilidou, S Pablo Sardi, Leonidas Stefanis, Kostas Vekrellis
Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's Disease (PD) and are associated with decreased Glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system (CNS) suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein, a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes...
March 14, 2018: Human Molecular Genetics
Weiming Wu, Jiugou Leng, Hailong Mei, Shubin Yang
Defect-rich, boron (B) and nitrogen (N) dual-doped and inert BN covalent bonds-free graphenes (BNGs) can be successfully synthesized via a method of two-step doping combined with chemical etching. B and N doping degree and surface areas of BNGs can be enhanced facilely by chemical etching without forming inert covalent BN bonds. The as-obtained porous BNGs deliver more superior electro-catalytic activity for oxygen reduction reaction than the unetched BNGs and commercial Pt/C catalysts.
March 8, 2018: Journal of Colloid and Interface Science
Matthieu Fumagalli, Julien Berriot, Benoit de Gaudemaris, Anne Veyland, Jean-Luc Putaux, Sonia Molina-Boisseau, Laurent Heux
Rubber materials with well-dispersed fillers and large mechanical reinforcement have been obtained by melt-processing a diene elastomer matrix and tailored nanocellulose powders having both a high specific surface area and a modified interface. Such filler powders with a specific surface area of 180 m2 g-1 and 100 m2 g-1 have been obtained by freeze-drying suspensions of short needle-like cellulose nanocrystals (CNCs) and entangled networks of microfibrillated cellulose (MFC) in tert-butanol/water, respectively...
March 16, 2018: Soft Matter
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